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Glioma

40% of all cancers spread to the brain

What is a glioma brain tumour?

A glioma is a type of brain tumour that has developed from cells that should have become healthy glial cells in the brain. Glioma brain tumours vary across the spectrum of low-grade (slow-growing) and to high-grade (faster-growing) and a poorer prognosis than low-grade.

What is a mixed glioma?

A mixed glioma is a glioma brain tumour that contains a mix of glial cells including astrocytes, oligodendrocytes and ependymal cells.

What is a glial cell?

Glial cells form a web of connective tissue to support the neurons (nerve cells) within the brain and spinal cord. Types of glial cells include astrocytes, oligodendrocytes, microglia and ependymal cells.

Glial cells play a multitude of roles in the brain. This includes a number of influences on synapses (the spaces that form connections between neurons) where the electrical impulses are converted into chemical messengers.

Astrocytes are key to brain health, information processing and vital for memory and learning.

Ependymal cells are essential for creating the passageways that contain cerebral spinal fluid (CSF), helping protect the brain and spinal cord and provide a key role in dispersing signalling molecules that support brain health.

Microglia  help with the immune system and protect the brain from toxins. These cells are important for the health and development of synapses in the brain – essential for the transmission of information across the nervous system.

Oligodendrocytes supply energy to neurons via the myelin sheath.

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Why are there different names for different types of glioma brain tumours?

All glioma brain tumours tend to be named to reflect the type of cells that make up the majority of the tumour.

This is determined through a biopsy or a surgical operation where a sample of the tumour is viewed by clinicians through a microscope (known as histopathological assessment) and classified by the physical characteristics that can be observed (known as the phenotype).

Some glioma brain tumours have different names depending upon their grade: for example they may be called a low-grade glioma or a grade 4 glioblastoma multiforme (GBM).

Astrocytoma, oligodendroglioma and ependymoma brain tumours are all classified as glioma tumours because they develop from glial cells that should have become healthy astrocytes, oligodendrocytes and ependymal cells. 

In some cases, a tumour may be called a mixed glioma brain tumour because it contains a mixture of these different cells.

Some glioma brain tumours may also be named after the position in which they are primarily growing – for example, a frontal lobe glioma, an optic nerve glioma or a brain stem glioma

As we learn more about brain tumours, names have sometimes changed to reflect not only the position and type of cells that they contain, but also the way that the tumour cells are growing and the expected behaviour of the tumour.

For example, a diffuse intrinsic pontine glioma (DIPG) is the term now commonly used to describe what used to be called a high-grade brain stem glioma in children. 

It reflects the fact that the tumour is “diffuse” in nature, meaning that it doesn’t have a clear boundary but instead spreads between and around surrounding brain cells, whilst the “pons” is the lowest, stem-like part of the brain at the top of the spinal cord.

Shared genetic characteristics are examined as part of glioma tumour classification. (This is known as the genotype of a brain tumour.) 

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Is glioma a low-grade (benign) or high-grade (malignant) brain tumour?

The grade of a glioma brain tumour gives an indication as to how the tumour is expected to behave (develop).

All brain and central nervous system (CNS) tumours are divided into four tumour types – grades 1 to 4. These grades are based on cells examined using a microscope as well as genetic and epigenetic changes that are discovered during molecular testing in a laboratory.

Grade 1 glioma (low-grade glioma): Grade 1 gliomas are usually occur in children and teenagers. They are the most slow-growing (low-grade) form of glioma brain tumour and carry the longest prognosis. The most common form of low-grade glioma is a pilocytic astrocytoma, which rarely progresses to a higher grade and can sometimes be completely removed by surgery .

Grade 2 glioma (low-grade glioma): Grade 2 gliomas are more common in adults but can also occur in children and teenagers. They are initially a slow-growing (low-grade) form of brain tumour but have a tendency to progress to a higher grade over time – usually a number of years. As prognosis varies between individuals, patients’ clinicians are best-placed to advise how long this process may take.

Oligodendroglioma and oligoastrocytomas tumours are often classified as grade 2 gliomas.

Grade 2 astrocytomas are sometimes also referred to as diffuse astrocytomas because they infiltrate through the brain. This is due to the nature of astrocytoma cells, which reach between and around the neurons.

Grade 3 glioma (anaplastic glioma): Anaplastic means that the glioma brain tumour cells are dividing rapidly . Anaplastic gliomas, also called grade 3 gliomas, are classed as a malignant form of brain cancer. They often spread to other parts of the brain and are more challenging to treat than low-grade gliomas.

Grade 4 glioma (glioblastoma multiforme): A glioblastoma multiforme (GBM) brain tumour may have developed from a lower grade of glioma, but the name changes once it is classified as high-grade. This is to reflect the fact that a grade 4 glioma usually has a mixture of cancerous cells within it, primarily astrocytoma and oligodendroglioma cells.

You can read more about glioblastoma multiforme (GBM) tumours here.

What symptoms are associated with glioma brain tumours?

Due to the range of different types of glioma brain tumours, we recommend you visit our brain tumour symptoms page.

What causes a glioma brain tumour?

We need to fund more research in order to understand how gliomas and other brain tumours are caused.

No single, definitive cause has yet been identified for brain tumours. Some risk factors have been identified, but due to the complex and unique health history for each patient, scientists are still unable to answer this fundamental question.

When glial cells form a glioma tumour, damage can be seen in the DNA and for example they no longer undergo apoptosis, which means programmed or purposeful cell death.

Discover more about risk factors for glioma and other brain tumours.

What is molecular testing and what do molecular markers of glioma brain tumours mean?

Current UK guidelines for the classification of gliomas defined by NICE (the National Institute for Clinical Excellence) state that tumours should also be tested for various molecular markers.

These markers include:

  • IDH1 and IDH2 mutations
  • ATRX mutations to identify IDH mutant astrocytomas and glioblastomas
  • 1p/19q codeletion to identify oligodendrogliomas
  • histone H3.3 K27M mutations in midline gliomas 
  • BRAF fusion and gene mutation to identify pilocytic astrocytoma 

In addition, clinicians should:

  • Test all high-grade glioma specimens for MGMT promoter methylation to inform prognosis and guide treatment
  • Consider testing IDH-wildtype glioma specimens for TERT promoter mutations to inform prognosis

IDH1 and IDH2 status: IDH stands for “Isocitrate Dehydrogenase.” This is an enzyme involved in the production of energy by brain tumour cells, and in GBM it may have a mutation that confers a better prognosis. Research has indicated that different forms of gliomas have differences between these enzymes, though their exact role is still being explored, as are drugs that can potentially influence IDH enzymes .

IDH 'wild' type status: This forms about 90% of GBM brain tumours  and usually indicates that the tumour formed as glioblastoma since the very beginning (primary GBM) and carries a worse prognosis than those classified as being IDH mutant.

IDH mutant: The IDH mutant category represents approximately 10% of GBMs , and indicates a secondary glioblastoma tumour, meaning that it was previously a lower grade glioma and carries a better prognosis than a 'wild' type status. 

ATRX mutations: The ATRX gene provides instructions for making a protein that plays an essential role in normal brain development. If the ATRX protein is mutated and doesn’t function properly, it can contribute to the development of certain types of glioma brain tumour. 

IDH NOS: This stands for “Not Otherwise Specified”, meaning that in rare cases, it cannot be determined whether a GBM is 'wild' type or mutant for IDH.

1p/19q deletion: The refers to missing genes on chromosomes , and tumours with this “deletion” may respond better to certain chemotherapy drugs such as Temozolomide or Carmustine. 

Histone H3.3 K27M mutations in diffuse midline gliomas: A histone is a type of protein that is found in chromosomes, and mutations in this protein can help identify diffuse midline gliomas and guide treatment. 

BRAF fusion and gene mutation in pilocytic astrocytoma: The BRAF gene can become fused with a number of different proteins, or undergo other mutations that are found in pilocytic astrocytoma brain tumours. In particular, the fusion of BRAF and KIAA1549 proteins is a diagnostic marker for this tumour type. 

MGMT methylation: This is short for O6-methylguanine-DNA methyltransferase and whether it is 'methylated' or 'unmethylated' indicates how effectively the tumour cells can repair the damage inflicted on them by certain chemotherapy drugs, such as Temozolomide. Patients with higher levels of MGMT methylation respond better to Temozolomide treatment.  Methylation means the transfer of a methyl group (CH3) from one molecule to another, which affects the way the tumour behaves.

TERT promoter mutations in glioma brain tumours: TERT stands for “telomerase reverse transcriptase.” It is an enzyme that affects telomere length in human cancers including glioma. Telomeres are structures at the end of chromosomes that can indicate expected lifespan. Unfortunately, long relative telomere length combined with TERT promoter mutations indicate that the glioma is likely to be resistant to radiotherapy, and hence the prognosis is worse than for gliomas without this genetic marker.

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How can we find a cure for gliomas?

Research we are funding across all of our Centres of Excellence will help lead towards finding a cure for glioma brain tumours.

Pioneering research at our Brain Tumour Research Centre of Excellence at Queen Mary University of London is focused on using GBM stem cells to help develop unique, patient-specific treatments.

Our team at the University of Plymouth Low-Grade Brain Tumour Centre of Excellence are researching a range of mutations in brain tumour cells that initiate tumour progression and drive growth, transforming slow-growing low-grade gliomas into high-grade gliomas. Their discoveries are designed to enable new treatments to be developed and tested in order to halt and hopefully reverse this process. The team are also testing combination therapies for low-grade brain tumours, designed to enhance the effectiveness of existing treatments.

The team of research and clinical experts at our Centre of Excellence at Imperial College, London, are part of a global collaboration looking at how the ketogenic diet can influence glioma metabolism and help in the effective treatment and management of living with this brain tumour.

Scientists at our Centre of Excellence in the University of Portsmouth are looking at mitochondria in glioblastomas, exploring ways to ‘shut down’ these ‘batteries’ that supply energy to the brain tumours.

We also fund BRAIN UK at Southampton University, the country’s only national tissue bank registry providing crucial access to brain tumour samples for researchers from all clinical neuroscience centres in the UK, effectively covering about 90% of the UK population, and an essential component in the fight to find a cure for glioma brain tumours.

Page last updated in November 2018. Next review September 2019.

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